Endocrinology, Vol 127, 2592-2594, Copyright © 1990 by Endocrine Society

ARTICLES

Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse

R Felix, MG Cecchini and H Fleisch
Department of Pathophysiology, University of Berne, Switzerland.

The op/op variant of murine osteopetrosis is a recessive mutation characterized by impaired bone resorption due to lack of osteoclasts. Cultured osteoblasts and fibroblasts from this mutant do not secrete M- CSF activity and resident macrophages are absent in bone marrow. This failure has been related to a mutation within the M-CSF coding region. We report now that the administration of recombinant human M-CSF (rhM- CSF) corrects in vivo the impaired bone resorption in this animal. The treatment restores the bone marrow cavity virtually absent in the op/op animal and induces the appearance of resorbing osteoclasts and of resident bone marrow macrophages. This proves that the deficiency of M- CSF is the cause of the op/op bone disorder and that this cytokine is directly or indirectly necessary for physiological osteoclastogenesis, the resulting bone resorption and for the establishment of bone marrow hemopoiesis.

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